Staphylococcus aureus is a nosocomial as well as a community-acquired pathogen, which causes a wide range of diseases and conditions, from minor skin infections to serious life-threatening conditions such as bacteraemia, endocarditis, pneumonia, toxic shock syndrome and wound infections. See Lowy et al., 1998, N. Engl. J. Med. 339:520-32. Additional examples of diseases and conditions caused by S. aureus include botryomyosis, bullous impetigo, carbuncle, cellulitis, central nervous system infections, folliculitis, furuncle, impetigo, infective and inflammatory eye disease, osteomyelitis and other infections of joints and bones, respiratory tract infections, and scalded skin syndrome. See The Staphylococci in Human Disease, Crossley and Archer (eds.), Churchill Livingstone Inc. 1997.
The worldwide growing incidence of staphylococcal infections is strongly related to an increased use of surgical devices and a growing number of immunocompromised patients. The situation has become more serious since the increased use of antibiotics has led to the emergence of methicillin-resistant S. aureus strains (MRSA). See Selvey et al., 2000, Infect. Control. Hosp. Epidemiol. 21:645-8; Peacock et al., 1980, Ann. Intern. Med. 93:526-32. More recently, S. aureus isolates with reduced susceptibility to vancomycin, the antibiotic of choice against MRSA strains, and isolates with vancomycin-resistance have been described. See Tenover et al., 2001, Emerg. Infect. Dis. 7:327-32; Tenover et al., 1998, J. Clin. Microbiol. 36:1020-7; and Palazzo et al., 2005, J. Clin. Microbial. 43:179-85. The rising emergence of multidrug-resistant staphylococci has led to a growing interest in the development of alternative approaches to prevent and treat staphylococcal infections.
Examples of polysaccharides that have been employed as possible vaccine components include S. aureus type 5 and type 8 capsular polysaccharides. See Shinefield et al., 2002, N. Eng. J. Med. 346:491-496. Examples of polypeptides that have been employed as possible vaccine components include clumping factor, collagen adhesin, and fibrinogen binding proteins. See Mamo et al., 1994, FEMS Immunol. Med. Mic. 10:47-54; Nilsson et al., 1998, J. Clin. Invest. 101:2640-2649; Josefsson et al., 2001, J. Infect. Dis. 184:1572-1580.
Much effort has been made in identifying additional S. aureus antigens for use in vaccines. Methods for identifying such antigens have included identifying S. aureus polypeptide sequences from sequencing the S. aureus genome (see Kuroda et al., 2001, Lancet 357:1225-1240; Baba et al., 2000, Lancet 359:1819-1827; European Patent Publication EP 0786519) including the use of bioinformatics to characterize polypeptide sequences obtained from genome sequencing (see, e.g., European Patent Publication EP 0786519); employing techniques such as those involving display technology and sera from infected patients (see, e.g., International Publication Nos. WO 01/98499 and WO 02/059148; and Etz et al., 2002, Proc. Natl. Acad. Sci. USA 99:6573-6578); and technologies, like proteomics (see Brady et al., 2006, Infect. Immun., 74:3415-26; Gatlin et al., 2006, Proteomics 6:1530-49; Pieper et al., 2006, Proteomics 6:4246-58; Vytvytska et al., 2002, Proteomics 2:580-90; Nandakumar et al., 2005, J. Proteome Res., 4:250-7) or protein selection methods based on expression libraries (see Clarke et al., 2006, J. Infect. Dis. 193:1098-108; Etz et al., 2002, Proc. Natl. Acad. Sci. USA 99:6573-8; Weichhart et al., 2003, Infect. Immun. 71:4633-41; and Yang et al., 2006, Vaccine 24:1117-23).
Citation or identification of any reference in this section or any other section of this application shall not be construed as an indication that such reference is available as prior art to the present invention.